Don't be hasty in clinical research decisions
The ability to use good judgment and make sound decisions in clinical research is based on experience, communication and execution. Decision making is influenced by such factors as the familiarization with regulations that govern clinical research, successful management of investigational site relationships and corrective and preventative action with issues that affect patient safety and credible data (informed consent, protocol deviations, safety reporting).
Exposure to these issues during a study improves the means to critically assess. It elevates perception from the immediate, reactionary view to the 10,000-foot global view. It forces us to look beyond what is before us to consider all aspects that will strengthen and resolve our position.
During a pre-study assessment visit many years ago, the experience I acquired from a diversity of clinical research and site management situations enabled me to look beyond immediate, negative information and consider the larger picture of true site competency. The evidence confirmed my decision to select a strong investigational site based on all factors. I did not limit myself solely to the subjective data provided.
Global thinking to promote critical analysis during monitoring visits:
- When dealing with protocol deviations at the site level, don’t react quickly or rashly to the initial discovery. Investigate what led to the deviation, the circumstances of the deviation and site execution upon discovery or notification of the deviation. The path to resolution is as important as discovery of the issue.
- If you are given negative site information prior to a site assessment visit, consider the data provided, the source of the data and the circumstances of the data. Objectively gather facts. The evidence will lead to the right answer.
I was tasked to conduct a pre-study assessment visit at a large academic center. While reviewing the site feasibility database, I noticed the site had been classified in a lower tier category, without justification for the status. Despite inquires to the clinical study team, I could not confirm a substantial reason for the categorization. Though this perplexed me, I continued my preparation for the selection visit. On the flight to the meeting, the low site tiering kept bothering at me. Something did not feel right and I needed to discover why.
There are many factors that contribute to the tier classification of investigational sites: historical enrollment performance, therapeutic experience, protocol deviations and latent data. The classification is usually accompanied by information to justify the categorization. However, this particular site classification was accompanied by zero data, which made the low tier questionable. The information at hand had alerted, but not necessarily influenced, my radar. It was my responsibility to perform an unbiased assessment of their experience, personnel and equipment to determine competency for study participation. I needed to think globally, without reacting immediately.
I arrived at the site and was greeted by a pleasant, serious young man. I asked if he had worked previously with this sponsor/CRO and a troubled look crossed his face. His subsequent candor set the transparency for the rest of the monitoring visit.
He informed me that, though they had initially been approached about the study several months back, the inquiry had ultimately been retracted by someone from the study team who deemed the site “a wrong fit” (in no uncertain terms). The study director had been told this directly. My expression of surprise at his disclosure prompted further explanation. It seems a previous trial with the sponsor had not gone well due to an inexperienced study coordinator no longer employed at the institution. The issues did not involve patient safety, but lack of motivation to recruit patients, enter data (by the former study coordinator) and update GCP training.
As soon as this was brought to the attention of the director, the study coordinator was replaced and guidelines implemented to prevent further occurrence. This included weekly research staff meetings to discuss enrollment, data entry and monitoring visit issues. All study staff were required to have at least one year of research experience, accompanied by a health science degree or medical background. The monthly departmental meetings included information regarding open trials to induce recruitment assistance from the treating physicians and large practices at the institution. All research staff were required to take annual GCP training through a validated third party, and all training was tracked and documented. Most importantly, the workload of all research coordinators was closely monitored to ensure a correct balance of study and patient assignment.
I had encountered similar issues at previously assessed sites, but issue identification was rarely followed by the level of corrective action demonstrated by this site. The director’s full disclosure was refreshing and unexpected. His analysis was informative; however, the manner by which their status had been communicated was inappropriate and I apologized for the way the situation was handled.
During the facility tour, I verified organized and sustainable practices. There was a dedicated research lab for processing and shipment. I was shown a dedicated research pharmacy with 24 hour drug temperature monitoring systems and electronic drug accountability database. A dedicated research examination room with calibrated, modern equipment was also present.
The candid discussion with the study director regarding prior deficiencies and corrective action allayed any concern regarding the site. My experience with issue identification and resolution (both my error and site error) gave me the correct insight to confirm the cycle of “lessons learned” by this particular research group, and feel confident in recommending them for study participation, despite an ambiguous red flag.
Elizabeth Blair Weeks-Rowe, LVN, CCRA, has spent nearly 14 years in a variety of clinical research roles including CRA, CRA trainer, CRA manager and clinical research writer. Currently she works in relationship development/study startup in the CRO industry. Email firstname.lastname@example.org.
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